Cross-sectional study finds no significant differences in serum DAO levels between cluster headache patients and controls, suggesting limited role of histamine metabolism.
Background: Diamine oxidase (DAO) is the main enzyme responsible for the extracellular degradation of histamine, thereby playing a key role in maintaining histamine balance. Oral DAO supplementation has been associated with decreased attack duration and frequency in a subgroup of patients with migraine. In contrast, the role of DAO in cluster headache (CH) remains largely unexplored. Notably, exogenous histamine is known to trigger cluster attacks in susceptible individuals, and histamine dysregulation has been proposed as a potential contributor to CH pathogenesis. This study aimed to quantify serum DAO activity in patients with cluster headache compared to healthy controls. Methods: We conducted a cross-sectional case–control study including 22 patients diagnosed with episodic and chronic cluster headache (mean age 47.9 ± 12.3 years; 19 males and 3 females; 20 episodic and 2 chronic CH) and 15 healthy controls (mean age 51.7 ± 12.0 years). Serum DAO activity was quantified by IDKⓇ DAO ELISA kit; low DAO levels were defined as <10 U/mL, a severe histamine intolerance was defined as DAO levels below 3 U/mL. Group differences were assessed using t-tests for continuous variables and chi-square tests for categorical variables. Correlations between DAO and clinical or demographic variables were evaluated with Pearson coefficients. Results: No difference was found in DAO levels between cluster headache patients and controls. No participants in the study exhibited histamine intolerance. Interestingly, 27% of CH patients showed DAO activity in the range of 3 to 10 U/mL, suggesting a probable histamine intolerance. When dichotomizing DAO levels (<10 U/mL vs ≥10 U/mL), no significant association with the diagnostic group was found, neither by chi-square tests nor logistic regression. Multinomial logistic regression further confirmed no significant association between DAO (continuous or dichotomized) and headache subtype. Conclusions: In this exploratory study, no significant difference was found between serum DAO activity between cluster headache patients and controls. These findings do not support a major role for DAO deficiency in the pathophysiology of cluster headache. However, the observed presence of low DAO activity in a subset of patients highlights the need for further studies with larger cohorts to clarify the potential involvement of histamine metabolism.
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Società Italiana per lo Studio delle Cefalee (2025) studied this question.
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